title: Detection of targeted perfluorocarbon nanoparticle binding using 19F diffusion weighted MR spectroscopy.
abstract: Real-time detection of targeted contrast agent binding is challenging due to background signal from unbound agent. (19)F diffusion weighted MR spectroscopy (DWS) could selectively detect binding of angiogenesis-targeted perfluorocarbon nanoparticles in vivo. Transgenic K14-HPV16 mice with epidermal squamous carcinomas exhibiting up-regulated neovasculature were used, with nontransgenic littermates as controls. Mice were treated with alpha(v)beta(3)-integrin targeted perfluorocarbon nanoparticles. (19)F DWS (b-values from 0 to 16,000 s/mm(2)) was performed on mouse ears in vivo at 11.74 Tesla. Progressive decay of (19)F signal with increased diffusion weighting at low b-values (< 1500 s/mm(2)) was observed in ears of both K14-HPV16 and control mice, demonstrating suppression of background (19)F signal from unbound nanoparticles in the blood. Much of the (19)F signal from ears of K14-HPV16 mice persisted at high b-values, indicating a stationary signal source, reflecting abundant nanoparticle binding to angiogenesis. (19)F signal in controls decayed completely at high b-values (> 1500 s/mm(2)), reflecting a moving signal source due to absence of angiogenesis (no binding sites). Estimated ADCs of nanoparticles in K14-HPV16 and control mice were 33.1 +/- 12.9 microm(2)/s and 19563 +/- 5858 microm(2)/s (p < 0.01). In vivo (19)F DWS can be used for specific detection of bound perfluorocarbon nanoparticles by selectively suppressing background (19)F signal from nanoparticles flowing in blood.
authors.affiliation: Department of Medicine, Division of Cardiology, Washington University Medical School, St Louis, Missouri, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Waters
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yang
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Robert
authors.initials: R
authors.lastname: Neumann
authors.forename: Andrea
authors.initials: A
authors.lastname: Santeford
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Arbeit
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
mesh_terms: D003287:Contrast Media / Q000737:chemistry; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015336:Molecular Probe Techniques; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D005462:Fluorine Radioisotopes; D005466:Fluorocarbons; D005682:Gadolinium